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Risky behaviors and Parkinson’s disease: A Mendelian randomization study in up to 1 million study participants

View ORCID ProfileSandeep Grover, Greco M Fabiola Del, Meike Kasten, Christine Klein, Christina M. Lill, View ORCID ProfileInke R. König
doi: https://doi.org/10.1101/446807
Sandeep Grover
Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany, sandeep.grover@imbs.uni-luebeck.de
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  • For correspondence: sandeep.grover@imbs.uni-luebeck.de
Greco M Fabiola Del
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Meike Kasten
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Christine Klein
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Christina M. Lill
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Inke R. König
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  • For correspondence: inke.koenig@imbs.uni-luebeck.de
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Abstract

Objective Dopaminergic neurotransmission is known to be a potential modulator of risky behaviors including substance abuse, promiscuity, and gambling. Furthermore, observational studies have shown associations between risky behaviors and Parkinson’s disease; however, the causal nature of these associations remains unclear. Thus, in this study, we examine causal associations between risky behavior phenotypes on Parkinson’s disease using a Mendelian randomization approach.

Methods We used two-sample Mendelian randomization to generate unconfounded estimates using summary statistics from two independent, large meta-analyses of genome-wide association studies on risk taking behaviors (n=370,771-939,908) and Parkinson’s disease (cases: n=9581, controls: n = 33,245). We used inverse variance weighted as the main method for judging causality.

Results Our results support a strong protective association between the tendency to smoke and Parkinson’s disease (OR=0.714 per log odds of ever smoking; 95% CI=0.568-0.897; p-value=0.0041; Cochran Q test; p-value=0.238; I2 index=6.3%). Furthermore, we observed risk association trends between automobile speed propensity as well as the number of sexual partners and Parkinson’s disease after removal of overlapping loci with other risky traits (OR=1.986 for each standard deviation increase in normalized automobile speed propensity; 95% CI=1.215-3.243; p-value=0.0066, OR=1.635 for each standard deviation increase in number of sexual partners; 95% CI=1.165-2.293; p-value=0.0049).

Interpretation These findings provide support for a causal relationship between general risk tolerance and Parkinson’s disease and may provide new insights in the pathogenic mechanisms leading to the development of Parkinson’s disease.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 02, 2018.
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Risky behaviors and Parkinson’s disease: A Mendelian randomization study in up to 1 million study participants
Sandeep Grover, Greco M Fabiola Del, Meike Kasten, Christine Klein, Christina M. Lill, Inke R. König
bioRxiv 446807; doi: https://doi.org/10.1101/446807
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Risky behaviors and Parkinson’s disease: A Mendelian randomization study in up to 1 million study participants
Sandeep Grover, Greco M Fabiola Del, Meike Kasten, Christine Klein, Christina M. Lill, Inke R. König
bioRxiv 446807; doi: https://doi.org/10.1101/446807

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